A primary objective in postmarketing drug safety surveillance is to ascertain the relationship between time-varying drug exposures and adverse events (AEs) related to health outcomes. Surveillance can be based on longitudinal observational databases (LODs), which contain time-stamped patient-level medical information including periods of drug exposure and dates of diagnoses. Due to its desirable properties, we focus on the self-controlled case series (SCCS) method for analysis in this context. SCCS implicitly controls for fixed multiplicative baseline covariates since each individual acts as their own control. In addition, only exposed cases are required for the analysis, which is computationally advantageous. In the first part of this work we present how the simple SCCS model can be applied to the surveillance problem, and compare the results of simple SCCS to those of existing methods. Many current surveillance methods are based on marginal associations between drug exposures and AEs. Such analyses ignore confounding drugs and interactions and have the potential to give misleading results. In order to avoid these difficulties, it is desirable for an analysis strategy to incorporate large numbers of time-varying potential confounders such as other drugs. In the second part of this work we propose the Bayesian multiple SCCS approach, which deals with high dimensionality and can provide a sparse solution via a Laplacian prior. We present details of the model and optimization procedure, as well as results of empirical investigations. SCCS is based on a conditional Poisson regression model, which assumes that events at different time points are conditionally independent given the covariate process. This requirement is problematic when the occurrence of an event can alter the future event risk. In a clinical setting, for example, patients who have a first myocardial infarction (MI) may be at higher subsequent risk for a second. In the third part of this work we propose the positive dependence self-controlled case series (PD-SCCS) method: a generalization of SCCS that allows the occurrence of an event to increase the future event risk, yet maintains the advantages of the original by controlling for fixed baseline covariates and relying solely on data from cases. We develop the model and compare the results of PD-SCCS and SCCS on example drug-AE pairs.